title: Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stromal cells expanded with fibroblast growth factor-2.
abstract: OBJECTIVE
  Human bone marrow mesenchymal stromal cells are useful in regenerative medicine for various diseases, but it remains unclear whether the aging of donors alters the multipotency of these cells. In this study, we examined age-related changes in the chondrogenic, osteogenic and adipogenic potential of mesenchymal stromal cells from 17 donors (25-81 years old), including patients with or without systemic vascular diseases.
  
  
  METHODS
  All stem cell lines were expanded with fibroblast growth factor-2 and then exposed to differentiation induction media. The chondrogenic potential was determined from the glycosaminoglycan content and the SOX9, collagen type 2 alpha 1 (COL2A1) and aggrecan (AGG) messenger RNA levels. The osteogenic potential was determined by monitoring the alkaline phosphatase activity and calcium content, and the adipogenic potential was determined from the glycerol-3-phosphate dehydrogenase activity and oil red O staining.
  
  
  RESULTS
  Systemic vascular diseases, including arteriosclerosis obliterans and Buerger disease, did not significantly affect the trilineage differentiation potential of the cells. Under these conditions, all chondrocyte markers examined, including the SOX9 messenger RNA level, showed age-related decline, whereas none of the osteoblast or adipocyte markers showed age-dependent changes.
  
  
  CONCLUSIONS
  The aging of donors from young adult to elderly selectively decreased the chondrogenic potential of mesenchymal stromal cells. This information will be useful in stromal cell-based therapy for cartilage-related diseases.
authors.affiliation: Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kanawa
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.forename: Veronica Sainik
authors.initials: VS
authors.lastname: Ronald
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Tania
authors.initials: T
authors.lastname: Saskianti
authors.forename: Haiou
authors.initials: H
authors.lastname: Pan
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; C499177:COL2A1 protein, human; D024043:Collagen Type II; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D016222:Fibroblast Growth Factor 2; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: aging; bone marrow; chondrocytes; differentiation; mesenchymal stromal cells